title: Nuclear-recessive mutations of factors involved in mitochondrial translation are responsible for age-related respiration deficiency of human skin fibroblasts.
abstract: We addressed the question of whether both mitochondrial and cytoplasmic translation activities decreased simultaneously in human skin fibroblasts with the age of the donors and found that the age-related reduction was limited to mitochondrial translation. Then, to determine which genome, mitochondrial or nuclear, was responsible for this age-related, mitochondria-specific reduction, pure nuclear transfer was carried out from mitochondrial DNA (mtDNA)-less HeLa cells to four fibroblast lines, two from aged subjects, one from a fetus, and one from a patient with cardiomyopathy, and their nuclear hybrid clones were isolated. A normal fibroblast line from the fetus and a respiration-deficient fibroblast line from the patient were used as a positive and a negative control, respectively. Subsequently, the mitochondrial translation and respiration properties of the nuclear hybrid clones were compared. A negative control experiment showed that this procedure could be used to isolate even nuclear hybrids expressing overall mitochondrial respiration deficiency, whereas no respiration deficiencies were observed in any nuclear hybrids irrespective of whether their mtDNAs were exclusively derived from aged or fetal donors. These observations suggest that nuclear-recessive mutations of factors involved in mitochondrial translation but not mtDNA mutations are responsible for age-related respiration deficiency of human fibroblasts.
authors.affiliation: Institute of Biological Sciences, University of Tsukuba, Ibaraki 305, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Isobe
authors.forename: S
authors.initials: S
authors.lastname: Ito
authors.forename: H
authors.initials: H
authors.lastname: Hosaka
authors.forename: Y
authors.initials: Y
authors.lastname: Iwamura
authors.forename: H
authors.initials: H
authors.lastname: Kondo
authors.forename: Y
authors.initials: Y
authors.lastname: Kagawa
authors.forename: J I
authors.initials: JI
authors.lastname: Hayashi
mesh_terms: D000375:Aging / Q000378:metabolism*; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D004272:DNA, Mitochondrial / Q000235:genetics*; D003576:Electron Transport Complex IV / Q000378:metabolism; D005347:Fibroblasts / Q000201:enzymology / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D009154:Mutation; D010100:Oxygen / Q000378:metabolism*; D014176:Protein Biosynthesis; D012867:Skin / Q000166:cytology / Q000201:enzymology / Q000378:metabolism*
chemical_list: D004272:DNA, Mitochondrial; D003576:Electron Transport Complex IV; D010100:Oxygen